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bioRxiv · 10.1101/2022.06.12.495812

Transit-amplifying progenitor with maturation-dependent behavior contributes to epidermal renewal

Ghuwalewala, S.·Jiang, K.·Ragi, S.·Shalloway, D.·Tumbar, T.
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Abstract

Transit-amplifying progenitor populations with phased behavior have long been postulated as essential to epidermal renewal, but not experimentally observed in vivo. Here we identify a population with bi-phasic behavior using CreER genetic cell-marking in mice for long-term lineage tracing and clonal analysis. Nascent, highly expressing Aspm cells undergo an amplification-phase followed by a timed transition into an extinction-phase, with near complete loss of descending cells from skin. Generalized birth-death modeling of Aspm-CreER and a Dlx1-CreER population that behaves like a stem cell demonstrates neutral competition for both populations, but neutral drift only for the stem cells. This work identifies a long-missing class of non-self-renewing epidermal progenitors with bi-phasic behavior that appears time-dependent as the lineage matures, indicative of a transit-amplifying cell. This has broad implications for understanding cell fate decisions and tissue renewal mechanisms. One-sentence summaryWe identify a long-missing class of non-self-renewing epidermal progenitors with bi-phasic and maturation-dependent behavior in vivo.

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Ghuwalewala, S., Jiang, K., Ragi, S., Shalloway, D., Tumbar, T.. 2022-06-15. Transit-amplifying progenitor with maturation-dependent behavior contributes to epidermal renewal. https://doi.org/10.1101/2022.06.12.495812

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